title: Chronic hyperaldosteronism in cryptochrome-null mice induces high-salt- and blood pressure-independent kidney damage in mice.
abstract: Although aldosterone has an essential role in controlling electrolyte and body fluid homeostasis, aldosterone also exerts certain pathological effects on the kidney. Several previous studies have attempted to examine these deleterious effects. However, the majority of these studies were performed using various injury models, including high-salt treatment and/or mineralocorticoid administration, by which the kidney changes observed were not only due to aldosterone but also due to prior injury caused by salt and hypertension. In the present study, we investigated aldosterone's pathological effect on the kidney using a mouse model with a high level of endogenous aldosterone. We used cryptochrome-null (Cry 1, 2 DKO) mice characterized by high aldosterone levels and low plasma renin activity and observed that even under normal salt exposure conditions, these mice showed increased albumin excretion and kidney tubular injury, decreased nephrin expression and increased reactive oxygen species production in the absence of hypertension. Exposure to high salt levels exacerbated the kidney damage observed in these mice. Moreover, we noted that decreasing blood pressure without blocking aldosterone action did not provide beneficial effects to the kidney in high-salt-treated Cry 1, 2 DKO mice. Thus, our findings support the hypothesis that aldosterone has deleterious effects on the kidney independent of high-salt exposure and high blood pressure.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Dwi Aris Agung
authors.initials: DA
authors.lastname: Nugrahaningsih
authors.affiliation: 1] Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan [2] Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Emoto
authors.affiliation: Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe, Japan.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vignon-Zellweger
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Eko
authors.initials: E
authors.lastname: Purnomo
authors.affiliation: Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yagi
authors.affiliation: 1] Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan [2] Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Department of System Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Doi
authors.affiliation: Department of System Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okamura
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirata
mesh_terms: D000450:Aldosterone / Q000097:blood / Q000235:genetics; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D056931:Cryptochromes / Q000235:genetics*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D006929:Hyperaldosteronism / Q000235:genetics* / Q000473:pathology*; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D017382:Reactive Oxygen Species / Q000378:metabolism; D012083:Renin / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D017673:Sodium Chloride, Dietary / Q000633:toxicity*; D015384:Zona Glomerulosa / Q000187:drug effects / Q000201:enzymology
chemical_list: D056931:Cryptochromes; D017382:Reactive Oxygen Species; D017673:Sodium Chloride, Dietary; D000450:Aldosterone; D012083:Renin